EP1002554A1 - Internal tissue medication permeating apparatus and method - Google Patents

Internal tissue medication permeating apparatus and method Download PDF

Info

Publication number
EP1002554A1
EP1002554A1 EP00102964A EP00102964A EP1002554A1 EP 1002554 A1 EP1002554 A1 EP 1002554A1 EP 00102964 A EP00102964 A EP 00102964A EP 00102964 A EP00102964 A EP 00102964A EP 1002554 A1 EP1002554 A1 EP 1002554A1
Authority
EP
European Patent Office
Prior art keywords
catheter
lumen
balloon
patient
liquid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP00102964A
Other languages
German (de)
French (fr)
Other versions
EP1002554B1 (en
Inventor
Andrew Jonathan Feiring
Original Assignee
FEIRING, Andrew Jonathan
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US520033 priority Critical
Priority to US07520033 priority patent/US5236413B1/en
Application filed by FEIRING, Andrew Jonathan filed Critical FEIRING, Andrew Jonathan
Priority to EP91909977A priority patent/EP0527920B1/en
Publication of EP1002554A1 publication Critical patent/EP1002554A1/en
Application granted granted Critical
Publication of EP1002554B1 publication Critical patent/EP1002554B1/en
Anticipated expiration legal-status Critical
Application status is Expired - Lifetime legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/104Balloon catheters used for angioplasty
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F11/00Methods or devices for treatment of the ears, e.g. surgical; Protective devices for the ears, carried on the body or in the hand; Non-electric hearing aids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/04Tracheal tubes
    • A61M16/0434Cuffs
    • A61M16/0436Special fillings therefor
    • A61M16/0438Liquid-filled
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/04Tracheal tubes
    • A61M16/0475Tracheal tubes having openings in the tube
    • A61M16/0477Tracheal tubes having openings in the tube with incorporated means for delivering or removing fluids
    • A61M16/0481Tracheal tubes having openings in the tube with incorporated means for delivering or removing fluids through the cuff wall
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/20Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A61N1/303Constructional details
    • A61N1/306Arrangements where at least part of the apparatus is introduced into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M2025/1043Balloon catheters with special features or adapted for special applications
    • A61M2025/105Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M2037/0007Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin

Abstract

An apparatus is described for selectively inducing the permeation of a liquid to a region of a stenosis in a blood vessel in a patient's body. The apparatus includes an external electrode (13) for positioning outside the patient's body and a catheter (10) carrying an internal electrode (38) for positioning adjacent a stenosis in a blood vessel in the body. The apparatus includes means for inducing an electric field between the internal electrode (38) and the external electrode (13) which is pulsed in phase with the patient's cardiac rhythm.

Description

    FIELD OF THE INVENTION
  • The present invention relates to techniques and devices for inducing the permeation of medication and the like into body tissue and organs.
  • BACKGROUND OF THE INVENTION
  • Iontophoresis has been utilized for many years for delivering medication into the body of a patient to diagnose and treat various ailments. Another related procedure iontohydrokinesis has been proposed for similar use. For example, iontophoresis has been utilized to deliver Pilocarpine medication to diagnose cystic fibrosis, for the permeation of insulin through the skin, the introduction of steroids into joints to treat arthritis, to anesthetize the eardrum or eye, to treat plantar warts with sodium salicylate, to treat canker sores in the mouth with steroids, to treat Peyronie's disease (the fibrosing of the penis), and to deliver procainamide across the heart during experimental open chest surgery in dogs.
  • Iontophoresis involves the transportation of medication in the form of naturally charged or ionic molecules by creating an electric field which acts as a driving force to cause the molecules to advance toward an oppositely charged pole. More particularly, iontophoresis is defined in Steadman's Medical Dictionary as the introduction by means of electric current of ions of soluble salts into the tissues of the body for therapeutic purposes; alternatively, the facilitated entry of electrically charged drugs into the surface tissue by application of an electric current. For example, if fluid having charged molecules is placed on a patient's skin and a properly oriented electric field is developed, the fluid will permeate the patient's skin. Where the molecules normally are uncharged, they may be rendered ionic by lowering or raising the pH of the carrying fluid.
  • The principle is similar for iontohydrokinesis which may be used to deliver uncharged, non-polar molecules of medication. In iontohydrokinesis, water, which has naturally charged molecules and containing noncharged or non-polar molecules of medication, is transported into the tissue of a patient. By subjecting the mixture to an electrical field, the water molecules will carry the uncharged particles with them as they flow from one pole towards the other.
  • Typically the technique for developing the electric field in iontophoresis or iontohydrokinesis involves placing both positive and negative electrodes externally of the patient's body or the specific organ that is to be treated. Consequently, the techniques do not lend themselves to targeted, localized treatment of internal body organs.
  • Generally, when it has been desired to use the procedure locally on an internal organ, it has been necessary to expose the organ surgically. Once the organ is exposed, the electrodes can be placed on opposite sides of the organ, as in the case of the delivery of procainamide to the heart during open chest surgery, discussed above. Such a surgical technique for localized treatment of internal organs has obvious drawbacks such as trauma to the patient and other disadvantages and risks of general surgery. It would be desirable, therefore, to provide a less invasive technique for delivering an effective concentration of medication locally to an internal organ. For example, it would be desirable to deliver concentrations of selected compounds to the wall of an artery as an adjunct to angioplasty, a procedure to enlarge a narrowed (stenosed) portion of an artery by placing a balloon in the stenosis and inflating the balloon to dilate the stenosis, thus improving blood flow through the artery.
  • A significant problem in angioplasty is the relatively high rate of restenosis (approximately 30%) after performing an initial angioplasty. It has been suggested that restenosis may be controlled or possibly prevented by applying suitable medication to the wall of the artery in the region of the angioplasty. For example, among the factors thought to contribute to incidence of restenosis is the uncontrolled proliferation of smooth muscle cells in the arterial wall, as a consequence of the angioplasty. To that end, it has been proposed that a concentrated dose of suitable medication, such as heparin, be applied to a local region of an artery and forced into the wall of the artery under pressure. A catheter adopted for that purpose is disclosed in U.S. Patent 4,636,195 issued January 13, 1987 to Wolinsky. The Wolinsky patent describes a catheter having a pair of spaced balloons mounted on the distal end of the catheter. The catheter is inserted into the patient's arteries and is navigated to the site of the angioplasty. The catheter is positioned so that the balloons embrace the region of the angioplasty. Suitable medication, such as heparin, then is forced, under pressure, into the space between the inflated balloons to force the medication, under pressure, into the wall of the artery.
  • It is among the objects of the invention, therefore, to provide a minimally evasive technique for delivering an effective concentration of medication or the like locally to an internal organ of the patient.
  • SUMMARY OF THE INVENTION
  • In accordance with the invention, medication or the like is cause to permeate through the tissue of a specific, targeted internal body organ using iontophoresis or iontohydrokinesis techniques. Practising the invention involves placing one or more electrodes externally of and circumferentially about the patient. Another electrode is inserted, as by a catheter, into the target organ or a selected portion of the organ. While an electric field is developed between the internal and external electrodes, medication having charged or polar molecules (iontophoresis) or uncharged molecules coupled with polar molecules, such as water (iontohydrokinesis), then may be delivered directly to the internal organ at a location between the internal and external electrodes. The electric field will cause the medication to permeate radially outwardly from the internal electrode toward the external electrodes thus causing the medication to permeate through the target organ.
  • One embodiment of the invention adapted for use in treating the wall of a blood vessel or other body lumen employs a balloon catheter which may be placed in the blood vessel and positioned by inflating the balloon in the specific portion to be treated. The catheter carries an internal electrode which may be in the form of an insulated wire extending through the catheter and terminating in the exposed electrode inside the balloon. The balloon which also acts as a drug reservoir has a plurality of regularly spaced minute pores. The interior of the inflatable balloon is in communication with a source of liquid medication by a lumen that extends through the catheter from the proximal end where the lumen can be connected to the liquid source. Medication (ionic or coupled to a charged liquid molecule) is delivered to the balloon and weeps through the minute pores during generation of the electric field. When used adjacent the heart, the electric field may be pulsed on during systole to reduce the risk of inducing cardiac arrhythmia.
  • It is among the objects of the invention to provide a method of inducing permeation of medication to a selected internal organ or body tissue.
  • Another object of the invention is to provide a method for treating a body organ with a substantial concentration of medicine or drugs, without systematically exposing the patent to such a concentration.
  • A further object of the invention is to provide a method and apparatus for permeating the wall of an artery with suitable medication so as to reduce the risk of restenosis after angioplasty as well as a primary treatment of obstructive coronary artery disease.
  • Another object of the invention is to provide a selective medication delivery technique for internal organs using principles of iontophoresis and iontohydrokinesis.
  • A further object of the invention is to utilize external electrodes and an electrode located in a targeted body organ for creating an electric field to induce the permeation of medication into the targeted body organ by iontophoresis or iontohydrokinesis.
  • DESCRIPTION OF THE DRAWINGS
  • The foregoing and other objects and advantages of the invention will be appreciated more fully from the further description thereof, with reference to the accompanying drawings wherein:
  • FIG. 1 is a diagrammatic illustration of a system for practising one embodiment of the invention including a balloon catheter having a permeable balloon and a "driving" electrode, and an external "return" electrode;
  • FIG. 2 is a cross-sectional illustration of the catheter shaft in a two lumen embodiment of the invention;
  • FIG. 2A is a cross-sectional illustration of the shaft of the catheter in a three lumen embodiment of the invention in which the balloon is in communication with two lumens including an inlet lumen and a return lumen;
  • FIG. 3 is an enlarged diagrammatic illustration of the catheter in accordance with the invention illustrating the balloon and electrode configuration at the distal end of the catheter;
  • FIG. 3A is an illustration similar to FIG. 3 illustrating the distal end of the catheter or a three lumen device of the type illustrated in FIG. 2A; and
  • FIG. 4 is a diagrammatic illustration of a patient having multiple electrodes placed circumferentially outside the body.
  • DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • FIG. 1 illustrates apparatus as it may be used in the practice of the invention. The apparatus includes a catheter 10 and an external return electrode 12. Although only one external electrode 20 is illustrated in FIG. 1, multiple external electrodes preferably are employed and are placed circumferentially about the patient as illustrated in FIG. 4.
  • As illustrated diagrammatically in FIG. 1, the catheter includes an elongate flexible shaft 12 that may be formed from any of a variety of polymeric materials commonly used in catheter manufacture. The catheter 10 has a proximal end (to the left in FIG. 1) that remains outside of the patient and a distal end (to the right in FIG. 1) that is inserted into the patient. An inflatable and deflatable balloon 14 is mounted to the distal end of the catheter shaft 12. The proximal end of the catheter shaft may branch out into two or three proximal legs including an inflation/deflation leg 16 and a guidewire leg 18 (in the two leg embodiment) and a third fluid return leg 20 (in the three leg embodiment). It should be noted that in the two leg embodiment, return leg 20 is omitted, all three legs 16, 18, 20 being shown in FIG. 1 for convenience of illustration. The catheter may have two or three lumens.
  • FIG. 2 illustrates, diagrammatically, the cross-sectional configuration of the catheter shaft 12 in a two leg, two lumen embodiment. In this embodiment, the catheter shaft 12 includes an inflation lumen 22 and a guidewire lumen 24. The inflation lumen 22 is in communication with the tubular inflation leg 16 which, in turn, is connected to an inflation/deflation device 26 which may be any of a variety of such devices as are commercially available. The distal end of the inflation lumen 22 opens into the interior of the balloon 14, as indicated diagrammatically at a port 28 in FIG. 3. Thus, the balloon 14 may be inflated and deflated through the lumen 22 by operation of the inflation/deflation device 26. As will be described in further detail, the balloon is formed to include a multiplicity of minute pores 30 which may be substantially regularly spaced about the surface of the balloon 14. The pores 30 serve to deliver the medication to the wall of the organ being treated. The other, larger lumen 24, is connected to the tubular guidewire leg 18 and serves to receive a guidewire 32. The guidewire lumen extends fully the length of the catheter shaft, and terminates at a distal exit orifice 34. The guidewire 32 thus can be projected distally beyond the distal end of the catheter shaft and may be manipulated to facilitate placement of the catheter in the body lumen as will be appreciated by those familiar with the art. For example, the guidewire may be of the steerable type as described in further detail in U.S. Patent 4,545,390 (Leary).
  • In order to develop the electrical field necessary for iontophoresis or iontohydrokinesis, the catheter includes a conductor that extends from the proximal end of the catheter to and into the balloon 14. In the illustrative embodiment, the conductor is in the form of an insulated wire 36 that may merge into the inflation/deflation lumen 22 at the proximal end of the catheter and may extend distally through the lumen 22 and into the balloon. The distal portion of the conductor 36 disposed within the balloon 14 may be uninsulated to define the inner, driving electrode. Preferably, the driving electrode is wrapped helically about the portion of the shaft 12A that extends through the balloon 14. The helical configuration of the electrode enhances uniform radial distribution of the electrical field. In alternative embodiments, the conductive wire may be conducted to one or more metallic band electrodes extending about the shaft within the balloon, for example, as to a mid-balloon marker band 38. Alternately, the electrode may be in the form of a wire mesh within the balloon about the catheter shaft.
  • In the three leg embodiment of the catheter, the catheter includes three lumens as indicated in FIG. 2A. In this embodiment, the catheter shaft 12A is formed to include an inflation lumen 22A, a guidewire lumen 24A and a return lumen 40. The proximal end of the return lumen 40 is connected to the tubular return leg 20 at the proximal end of the catheter. The distal end of the return lumen 40 opens into the interior of the balloon at a port 42 illustrated in FIG. 3A. As will be described further below, the three leg embodiment enables a continuous flow of liquid into and out of the balloon 14.
  • The size of the balloon 14 is selected so that when inflated it will be slightly larger than the body lumen into which the catheter is to be inserted. This is desirable in order that the balloon may be pressed lightly against the inner luminal surface of the targeted organ so that medication that is emitted from the balloon will be applied directly and intimately against the inner luminal surface of the organ. The minute pores 30 may be of the order of 400 angstroms to 25 microns in diameter. The balloon 14 preferably is made of an inelastic polymeric material of the type used in balloon angioplasty catheters as will be familiar to those skilled in the art. For example, the balloon may be formed from polyethylene terephthalate. The inelasticity of the balloon material serves to prevent the pores 30 from becoming too large during inflation of the balloon, thus undesirably varying the flow rate of the medication.
  • The external return electrodes 13 and the internal driving electrode are connected to a direct current source 44. In order to reduce the risk of disrupting the patient's heart rhythm when the electrodes are in the region of the heart, the current to the electrodes preferably is pulsed on during the systole phase of the cardiac pumping action and off during diastolic phase.
  • In use, the external electrodes 20 are positioned circumferentially about the patient. The catheter 10 is inserted into the patient and manipulated into the desired location of the desired body lumen. The catheter 10 may be positioned by any one of numerous well-known methods such as the use of guidewire 32. Once the catheter 10 has been advanced so that the balloon 14 is at the desired location, the balloon 14 is inflated to fill the body lumen and seal the balloon against the inner surface of the body lumen under light pressure. Preferably, the balloon is pressurized not substantially more than approximately 150 mmHg. Power to the electrodes is provided to develop an electric field radiating outward from the inner driving electrode to the outer return electrodes 20. Due to the charged nature of the medication or the water with which the medication may be mixed, the medication flows radially outward along the lines of the electric field, thus permeating the targeted tissue located radially outward from the balloon 14. The medication thus is localized to the target organ.
  • The external electrodes are positioned, as shown in FIG. 4, about the patient's exterior so that the medication will flow radially outward in all directions. The charge applied to each of the electrodes may be varied when the internal electrode is not located centrally inside the patient so that the field is of equal strength through 360°. The current strength, duration of current application and location of the eternal electrodes may be varied to further focus the flow of medication. Patch electrodes, which are known in the art, may be used as the eternal electrodes. Thus, the direction and uniformity of dispersion and permeation of the medication may be controlled. The polarity of the inner driving and eternal return electrode is selected with reference to the sense of the ionic compound to assure dispersion in a radially outward direction.
  • The method and apparatus of the present invention provide numerous advantages. By utilizing the electrode configuration of the present invention, specific internal locations of a patient may be targeted for treatment with a particular medication. Furthermore, the permeation of the medication into the body tissue eternal the balloon is induced by creating an electric field and not by increasing pressure on the liquid in the balloon 14. Consequently, mechanical stress to the body lumen is kept at a minimum. By introducing the medication to the balloon and only allowing it to pass radially outward through the balloon pores, an excessive concentration of medication is not introduced to the patient.
  • While the foregoing method and apparatus are applicable to a wide variety of body organs and lumens, they have particular use in blood vessels such as arteries. The catheter 10 shown in FIG. 1 may be used in the primary treatment of a lesion (stenosis) with an appropriate medication to reduce the size of the lesion or to prevent restenosis after an angioplasty. In primary treatment of a lesion, the catheter 10 is inserted into an artery until the balloon 14 is positioned against the region of the dilated stenosis. A suitable liquid medication (ionic or coupled to a polar carrier molecule) is infused into the balloon 14 to inflate the balloon and seal it against the luminal surface. An electric field then is induced between the internal driving electrode and the external return electrodes 13 so that the medication flows radially outward through the pores 30 of the balloon 14 and into the arterial wall to break down the stenotic material and cause reduction in the size of the stenosis.
  • When used for treating an artery after a conventional angioplasty to prevent restenosis, an antirestenosis drug, such as heparin, is used to inflate the balloon 14. Once the electric field has been induced, the heparin or other appropriate medication will flow outwardly and permeate the arterial wall. The degree to which the medication permeates the wall can be controlled by varying the strength of the electric field and the length of time that the electric field is maintained. In the illustrated catheter, the inflation of the balloon 14 shuts off blood flow through the artery during the procedure. The present method may be employed in an autoperfusion catheter of the type described in U.S. Patent 4,581,017 (Sahota) to allow blood flow through the catheter to distally perfuse the artery while the balloon is inflated. As described in that patent, the disclosure of which is hereby incorporated by reference in its entirety, an opening is provided in the catheter shaft wall proximally of the balloon to allow blood to perfuse through the catheter distally of the balloon.
  • It sometimes may occur that the ionic charge of the molecule may change during the procedure, for example, if the pH of the fluid changes. Such pH change may result from interaction of the liquid with the electrode as may be a function of the duration of the procedure. In order to avoid adverse changes in pH, the liquid may be aspirated periodically from the catheter and replaced with fresh liquid. This procedure may be used with the two lumen configuration described above and illustrated in FIGS. 1 and 2. Alternately with the three lumen embodiment, represented by FIG. 2A, a continuous flow of liquid may be established through the balloon, flow of liquid being toward and into the balloon through the inflation lumen 22A and out of and away from the balloon through the return lumen 40. The return leg 20 at the proximal end of the catheter 10 preferably is provided with a variable flow resistor 46 by which the back pressure of the returning outflowing liquid may be controlled. By operating the inflation device and variable restrictor 46, the pressure developed within the balloon and rate of continuous flow through the system may be controlled as desired.
  • Thus, I have described the invention by which medication may be applied selectively to a targeted internal organ or body lumen, such as an artery. It should be understood, while the invention has been described with regard to treatment of tissue adjacent a body lumen, the invention may be practiced in any location where it is desired to apply medication to a vessel or organ having a lumen accessible by a catheter. For example, the apparatus may be utilized to treat the heart or coronary arteries. The catheter may be passed into a lumen in a particular organ or may even be inserted into a lumen formed in an organ or tumor for the express purpose of receiving the catheter.
  • It should be understood that the foregoing description of the invention is intended merely to be illustrative thereof and that other embodiments, modifications and equivalents may be apparent to those skilled in the art without departing from its spirit.
  • Having thus described the invention, what I desire to claim in the letters patent is:

Claims (5)

  1. An apparatus for selectively inducing the permeation of liquid to a region of a stenosis in a blood vessel in the body of a patient, comprising at least one external electrode (13) for positioning of outside the patient's body; a catheter (10) having an elongate flexible shaft (12) having proximal and distal ends, an internal electrode (38) carried at the distal end of the catheter (10); a conductor (36) extending through the catheter shaft (12) and being electrically connected to the internal electrode (38), the proximal end of the conductor (36) being connectable to a source of electrical energy; and means (44) for inducing an electric field between said internal electrode (38) and said at least one external electrode (13) so that liquid emitted from the distal end of the catheter (10) will flow in a direction extending from the internally placed electrode (38) outwardly toward the external electrode (13);
    characterised in that the elongate flexible shaft (12) is dimensioned for insertion into the human vascular system such that it can be inserted into a blood vessel and positioned in the region of a stenosis in the blood vessel, the catheter (10) includes a lumen (22) extending along the shaft for delivering a liquid from the proximal to the distal region of the catheter, and further includes means (26) which contains and delivers the liquid having a compound to treat the region of the stenosis or to retard restenosis, and in that the means (44) for inducing an electric field is adapted to pulse the electric field in phase with the patient's cardiac rhythm.
  2. An apparatus as claimed in claim 1, wherein the external electrode (13) is adapted to extend circumferentially about a portion of the patient's body.
  3. An apparatus as claimed in claim 1 or claim 2, wherein the catheter (10) further comprises a lumen extending through the catheter shaft (12) and terminating in an outlet distally beyond a balloon (14) and means for directing blood flow through the lumen and out of the distal outlet to permit distal perfusion of blood during inflation of the balloon.
  4. An apparatus as claimed in any of claims 1-3, wherein the catheter (10) includes a second lumen (40) for the return of liquid from the distal to the proximal region of the catheter (10).
  5. An apparatus as claimed in claim 4, further comprising a variable flow resistor (46) to control the back pressure of liquid in the second lumen (40).
EP00102964A 1990-05-07 1991-05-06 Internal tissue medication permeating apparatus Expired - Lifetime EP1002554B1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US520033 1990-05-07
US07520033 US5236413B1 (en) 1990-05-07 1990-05-07 Method and apparatus for inducing the permeation of medication into internal tissue
EP91909977A EP0527920B1 (en) 1990-05-07 1991-05-06 Blood vessels medication permeating apparatus

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP91909977A Division EP0527920B1 (en) 1990-05-07 1991-05-06 Blood vessels medication permeating apparatus

Publications (2)

Publication Number Publication Date
EP1002554A1 true EP1002554A1 (en) 2000-05-24
EP1002554B1 EP1002554B1 (en) 2001-10-24

Family

ID=24070921

Family Applications (2)

Application Number Title Priority Date Filing Date
EP00102964A Expired - Lifetime EP1002554B1 (en) 1990-05-07 1991-05-06 Internal tissue medication permeating apparatus
EP91909977A Expired - Lifetime EP0527920B1 (en) 1990-05-07 1991-05-06 Blood vessels medication permeating apparatus

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP91909977A Expired - Lifetime EP0527920B1 (en) 1990-05-07 1991-05-06 Blood vessels medication permeating apparatus

Country Status (8)

Country Link
US (7) US5236413B1 (en)
EP (2) EP1002554B1 (en)
JP (1) JP3372250B2 (en)
AT (2) AT207375T (en)
AU (1) AU642020B2 (en)
CA (1) CA2081666C (en)
DE (4) DE69132787T2 (en)
WO (1) WO1991016945A1 (en)

Families Citing this family (447)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5236413B1 (en) * 1990-05-07 1996-06-18 Andrew J Feiring Method and apparatus for inducing the permeation of medication into internal tissue
US5458568A (en) * 1991-05-24 1995-10-17 Cortrak Medical, Inc. Porous balloon for selective dilatation and drug delivery
AU8074591A (en) * 1990-06-15 1992-01-07 Cortrak Medical, Inc. Drug delivery apparatus and method
US5499971A (en) * 1990-06-15 1996-03-19 Cortrak Medical, Inc. Method for iontophoretically delivering drug adjacent to a heart
US5498238A (en) * 1990-06-15 1996-03-12 Cortrak Medical, Inc. Simultaneous angioplasty and phoretic drug delivery
US5599296A (en) * 1991-02-14 1997-02-04 Wayne State University Apparatus and method of delivery of gas-supersaturated liquids
US5584803A (en) 1991-07-16 1996-12-17 Heartport, Inc. System for cardiac procedures
US5769812A (en) 1991-07-16 1998-06-23 Heartport, Inc. System for cardiac procedures
US5558644A (en) 1991-07-16 1996-09-24 Heartport, Inc. Retrograde delivery catheter and method for inducing cardioplegic arrest
US6482171B1 (en) 1991-07-16 2002-11-19 Heartport, Inc. Multi-lumen catheter
US5263925A (en) * 1991-07-22 1993-11-23 Gilmore Jr Thomas F Photopheresis blood treatment
CA2074304C (en) * 1991-08-02 1996-11-26 Cyril J. Schweich, Jr. Drug delivery catheter
US6224619B1 (en) 1991-12-17 2001-05-01 Heartport, Inc. Blood vessel occlusion trocar having size and shape varying insertion body
US5344398A (en) * 1992-02-25 1994-09-06 Japan Crescent, Inc. Heated balloon catheter
US5578008A (en) * 1992-04-22 1996-11-26 Japan Crescent, Inc. Heated balloon catheter
US5501662A (en) * 1992-05-22 1996-03-26 Genetronics, Inc. Implantable electroporation method and apparatus for drug and gene delivery
US6132419A (en) * 1992-05-22 2000-10-17 Genetronics, Inc. Electroporetic gene and drug therapy
US5507724A (en) * 1992-07-01 1996-04-16 Genetronics, Inc. Electroporation and iontophoresis apparatus and method for insertion of drugs and genes into cells
US5304120A (en) * 1992-07-01 1994-04-19 Btx Inc. Electroporation method and apparatus for insertion of drugs and genes into endothelial cells
WO1994003215A1 (en) * 1992-07-30 1994-02-17 Andrew Stone Dialysis system, method and filtrate solution composition
US5755968A (en) * 1992-07-30 1998-05-26 Stone; Andrew Dialysis system and method for removing toxic matter from the serum of the large intestine
US5688233A (en) * 1992-08-17 1997-11-18 Genetronics, Inc. Electronincorporation enhanced transdermal delivery of molecules
US5462520A (en) * 1992-08-17 1995-10-31 Genetronics, Inc. Transsurface drug delivery by electrofusion of microbubbles to the tissue surface
US5807306A (en) * 1992-11-09 1998-09-15 Cortrak Medical, Inc. Polymer matrix drug delivery apparatus
US5256141A (en) * 1992-12-22 1993-10-26 Nelson Gencheff Biological material deployment method and apparatus
US5401239A (en) * 1993-03-11 1995-03-28 Physion S.R.L. Electromotive treatment of catheter-rerelated infections
WO1994021320A1 (en) * 1993-03-15 1994-09-29 Advanced Cardiovascular Systems, Inc. Fluid delivery catheter
DE69637676D1 (en) * 1995-11-09 2008-10-23 Univ R Use of locally administered Lysine for IMPROVING vascular FUNCTION
US5891459A (en) * 1993-06-11 1999-04-06 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US5852058A (en) * 1993-06-11 1998-12-22 The Board Of Trustees Of The Leland Stanford Junior University Intramural delivery of nitric oxide enhancer for inhibiting lesion formation after vascular injury
US5861168A (en) * 1993-06-11 1999-01-19 The Board Of Trustees Of The Leland Stanford Junior University Intramural delivery of nitric oxide enhancer for inhibiting lesion formation after vascular injury
US5344402A (en) * 1993-06-30 1994-09-06 Cardiovascular Dynamics, Inc. Low profile perfusion catheter
US8321013B2 (en) 1996-01-08 2012-11-27 Impulse Dynamics, N.V. Electrical muscle controller and pacing with hemodynamic enhancement
US8825152B2 (en) 1996-01-08 2014-09-02 Impulse Dynamics, N.V. Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue
US9713723B2 (en) 1996-01-11 2017-07-25 Impulse Dynamics Nv Signal delivery through the right ventricular septum
IL148949D0 (en) * 1996-01-08 2002-11-10 Impulse Dynamics Nv Electrical muscle controller
US5634899A (en) * 1993-08-20 1997-06-03 Cortrak Medical, Inc. Simultaneous cardiac pacing and local drug delivery method
US5421818A (en) * 1993-10-18 1995-06-06 Inner Ear Medical Delivery Systems, Inc. Multi-functional inner ear treatment and diagnostic system
US5397307A (en) * 1993-12-07 1995-03-14 Schneider (Usa) Inc. Drug delivery PTCA catheter and method for drug delivery
US5419763B1 (en) * 1994-01-04 1997-07-15 Cor Trak Medical Inc Prostatic drug-delivery catheter
JP3403233B2 (en) * 1994-01-20 2003-05-06 テルモ株式会社 Balloon catheter
US5415636A (en) * 1994-04-13 1995-05-16 Schneider (Usa) Inc Dilation-drug delivery catheter
US5486160A (en) * 1994-05-04 1996-01-23 Physion S.R.L. Device and method for the combined electropharmacological treatment of the bladder and the prostatic urethra
US5478309A (en) 1994-05-27 1995-12-26 William P. Sweezer, Jr. Catheter system and method for providing cardiopulmonary bypass pump support during heart surgery
US5728068A (en) * 1994-06-14 1998-03-17 Cordis Corporation Multi-purpose balloon catheter
US5505700A (en) * 1994-06-14 1996-04-09 Cordis Corporation Electro-osmotic infusion catheter
US5681278A (en) * 1994-06-23 1997-10-28 Cormedics Corp. Coronary vasculature treatment method
US5900433A (en) * 1995-06-23 1999-05-04 Cormedics Corp. Vascular treatment method and apparatus
US6464697B1 (en) 1998-02-19 2002-10-15 Curon Medical, Inc. Stomach and adjoining tissue regions in the esophagus
US6440128B1 (en) 1998-01-14 2002-08-27 Curon Medical, Inc. Actively cooled electrode assemblies for forming lesions to treat dysfunction in sphincters and adjoining tissue regions
US6258087B1 (en) 1998-02-19 2001-07-10 Curon Medical, Inc. Expandable electrode assemblies for forming lesions to treat dysfunction in sphincters and adjoining tissue regions
US5681308A (en) * 1994-06-24 1997-10-28 Stuart D. Edwards Ablation apparatus for cardiac chambers
US8906010B2 (en) * 1998-02-19 2014-12-09 Mederi Therapeutics, Inc. Graphical user interface for association with an electrode structure deployed in contact with a tissue region
US7165551B2 (en) 1998-02-19 2007-01-23 Curon Medical, Inc. Apparatus to detect and treat aberrant myoelectric activity
US5575788A (en) * 1994-06-24 1996-11-19 Stuart D. Edwards Thin layer ablation apparatus
US6405732B1 (en) 1994-06-24 2002-06-18 Curon Medical, Inc. Method to treat gastric reflux via the detection and ablation of gastro-esophageal nerves and receptors
US6423058B1 (en) 1998-02-19 2002-07-23 Curon Medical, Inc. Assemblies to visualize and treat sphincters and adjoining tissue regions
US6056744A (en) * 1994-06-24 2000-05-02 Conway Stuart Medical, Inc. Sphincter treatment apparatus
US6402744B2 (en) 1998-02-19 2002-06-11 Curon Medical, Inc. Systems and methods for forming composite lesions to treat dysfunction in sphincters and adjoining tissue regions
US6009877A (en) 1994-06-24 2000-01-04 Edwards; Stuart D. Method for treating a sphincter
US6273886B1 (en) 1998-02-19 2001-08-14 Curon Medical, Inc. Integrated tissue heating and cooling apparatus
US6024743A (en) * 1994-06-24 2000-02-15 Edwards; Stuart D. Method and apparatus for selective treatment of the uterus
US6358245B1 (en) 1998-02-19 2002-03-19 Curon Medical, Inc. Graphical user interface for association with an electrode structure deployed in contact with a tissue region
US20030135206A1 (en) 1998-02-27 2003-07-17 Curon Medical, Inc. Method for treating a sphincter
AU752243B2 (en) 1998-02-19 2002-09-12 Curon Medical, Inc. Electrosurgical sphincter treatment apparatus
US6325798B1 (en) 1998-02-19 2001-12-04 Curon Medical, Inc. Vacuum-assisted systems and methods for treating sphincters and adjoining tissue regions
US6355031B1 (en) 1998-02-19 2002-03-12 Curon Medical, Inc. Control systems for multiple electrode arrays to create lesions in tissue regions at or near a sphincter
US5505730A (en) * 1994-06-24 1996-04-09 Stuart D. Edwards Thin layer ablation apparatus
US5514092A (en) * 1994-08-08 1996-05-07 Schneider (Usa) Inc. Drug delivery and dilatation-drug delivery catheters in a rapid exchange configuration
AUPM982694A0 (en) * 1994-12-02 1995-01-05 University Of Queensland, The Iontophoresis method and apparatus
US5569198A (en) * 1995-01-23 1996-10-29 Cortrak Medical Inc. Microporous catheter
US5749845A (en) * 1995-01-25 1998-05-12 Iotek, Inc. Delivering an agent to an organ
US5735817A (en) * 1995-05-19 1998-04-07 Shantha; T. R. Apparatus for transsphenoidal stimulation of the pituitary gland and adjoining brain structures
US5865801A (en) * 1995-07-18 1999-02-02 Houser; Russell A. Multiple compartmented balloon catheter with external pressure sensing
US6302875B1 (en) 1996-10-11 2001-10-16 Transvascular, Inc. Catheters and related devices for forming passageways between blood vessels or other anatomical structures
WO1997018855A1 (en) * 1995-11-21 1997-05-29 Eduard Naumovich Lerner Device for enhanced delivery of biologically active substances and compounds in an organism
US6913763B2 (en) * 1996-11-19 2005-07-05 Intrabrain International Nv Method and device for enhanced delivery of a biologically active agent through the spinal spaces into the central nervous system of a mammal
US6678553B2 (en) 1995-11-21 2004-01-13 Intraabrain International Nv Device for enhanced delivery of biologically active substances and compounds in an organism
US5779661A (en) * 1995-12-11 1998-07-14 Physion, S.R.L. Method of treating dysfunctional bladder syndromes by electromotive drug administration
EP0780139A1 (en) * 1995-12-22 1997-06-25 PHYSION S.r.l. Device for the combined electropharmacological treatment of the bladder and the prostatic urethra
US9289618B1 (en) 1996-01-08 2016-03-22 Impulse Dynamics Nv Electrical muscle controller
US7167748B2 (en) 1996-01-08 2007-01-23 Impulse Dynamics Nv Electrical muscle controller
US5895417A (en) * 1996-03-06 1999-04-20 Cardiac Pathways Corporation Deflectable loop design for a linear lesion ablation apparatus
US6015407A (en) * 1996-03-06 2000-01-18 Cardiac Pathways Corporation Combination linear ablation and cooled tip RF catheters
US5800482A (en) * 1996-03-06 1998-09-01 Cardiac Pathways Corporation Apparatus and method for linear lesion ablation
US6032077A (en) * 1996-03-06 2000-02-29 Cardiac Pathways Corporation Ablation catheter with electrical coupling via foam drenched with a conductive fluid
US5797903A (en) * 1996-04-12 1998-08-25 Ep Technologies, Inc. Tissue heating and ablation systems and methods using porous electrode structures with electrically conductive surfaces
EP0959933A1 (en) * 1996-05-03 1999-12-01 Emed Corporation Combined coronary stent deployment and local delivery of an agent
US8353908B2 (en) 1996-09-20 2013-01-15 Novasys Medical, Inc. Treatment of tissue in sphincters, sinuses, and orifices
US20040219660A1 (en) * 2001-12-14 2004-11-04 Dev Sukhendu B. Electroporation-mediated intravascular delivery
US5944710A (en) * 1996-06-24 1999-08-31 Genetronics, Inc. Electroporation-mediated intravascular delivery
US5709653A (en) * 1996-07-25 1998-01-20 Cordis Corporation Photodynamic therapy balloon catheter with microporous membrane
US5797868A (en) * 1996-07-25 1998-08-25 Cordis Corporation Photodynamic therapy balloon catheter
US5720775A (en) * 1996-07-31 1998-02-24 Cordis Corporation Percutaneous atrial line ablation catheter
US7840264B1 (en) 1996-08-19 2010-11-23 Mr3 Medical, Llc System and method for breaking reentry circuits by cooling cardiac tissue
US7908003B1 (en) 1996-08-19 2011-03-15 Mr3 Medical Llc System and method for treating ischemia by improving cardiac efficiency
US6066489A (en) * 1996-08-30 2000-05-23 Arrow International, Inc. Method for treating blood borne viral pathogens such as immunodeficiency virus
US5704908A (en) * 1996-10-10 1998-01-06 Genetronics, Inc. Electroporation and iontophoresis catheter with porous balloon
EP0835673A3 (en) * 1996-10-10 1998-09-23 Schneider (Usa) Inc., Catheter for tissue dilatation and drug delivery
US5722403A (en) * 1996-10-28 1998-03-03 Ep Technologies, Inc. Systems and methods using a porous electrode for ablating and visualizing interior tissue regions
US6059726A (en) * 1996-11-08 2000-05-09 The Regents Of The University Of California Method for locating the atrio-ventricular (AV) junction of the heart and injecting active substances therein
US6076012A (en) 1996-12-19 2000-06-13 Ep Technologies, Inc. Structures for supporting porous electrode elements
US6001094A (en) * 1997-01-09 1999-12-14 Vidacare International, Inc. Implantable soluble electrode system
US7048717B1 (en) 1999-09-27 2006-05-23 Essex Technology, Inc. Rotate-to-advance catheterization system
US5755687A (en) 1997-04-01 1998-05-26 Heartport, Inc. Methods and devices for occluding a patient's ascending aorta
US7027869B2 (en) 1998-01-07 2006-04-11 Asthmatx, Inc. Method for treating an asthma attack
US8251070B2 (en) 2000-03-27 2012-08-28 Asthmatx, Inc. Methods for treating airways
US6488673B1 (en) * 1997-04-07 2002-12-03 Broncus Technologies, Inc. Method of increasing gas exchange of a lung
US7921855B2 (en) 1998-01-07 2011-04-12 Asthmatx, Inc. Method for treating an asthma attack
US6634363B1 (en) 1997-04-07 2003-10-21 Broncus Technologies, Inc. Methods of treating lungs having reversible obstructive pulmonary disease
US7992572B2 (en) 1998-06-10 2011-08-09 Asthmatx, Inc. Methods of evaluating individuals having reversible obstructive pulmonary disease
US8181656B2 (en) 1998-06-10 2012-05-22 Asthmatx, Inc. Methods for treating airways
US6045528A (en) * 1997-06-13 2000-04-04 Intraear, Inc. Inner ear fluid transfer and diagnostic system
BR9810372A (en) 1997-06-30 2000-09-05 Rhone Poulenc Rorer Sa nucleic acid transfer process for inner cell bodies of multicellular eukaryotes in vivo, composition, and nucleic acid electric field and product combination
WO1999001158A1 (en) 1997-06-30 1999-01-14 Rhone-Poulenc Rorer S.A. Improved method for transferring nucleic acid into the striped muscle and combination therefor
US5997532A (en) * 1997-07-03 1999-12-07 Cardiac Pathways Corporation Ablation catheter tip with a buffer layer covering the electrode
US6241666B1 (en) 1997-07-03 2001-06-05 Cardiac Pathways Corp. Ablation catheter tip with a buffer layer covering the electrode
US6024740A (en) 1997-07-08 2000-02-15 The Regents Of The University Of California Circumferential ablation device assembly
ES2283020T3 (en) 1997-07-16 2007-10-16 Metacure Nv Smooth muscle controller.
US8346363B2 (en) 1999-03-05 2013-01-01 Metacure Limited Blood glucose level control
US6010500A (en) * 1997-07-21 2000-01-04 Cardiac Pathways Corporation Telescoping apparatus and method for linear lesion ablation
US9023031B2 (en) 1997-08-13 2015-05-05 Verathon Inc. Noninvasive devices, methods, and systems for modifying tissues
US5866561A (en) * 1997-08-21 1999-02-02 Scimed Life Systems, Inc. Local delivery of estrogen for angiogenesis
US5957901A (en) * 1997-10-14 1999-09-28 Merit Medical Systems, Inc. Catheter with improved spray pattern for pharmaco-mechanical thrombolysis therapy
US6042561A (en) * 1997-10-22 2000-03-28 Ash Medical Systems, Inc. Non-intravascular infusion access device
AU2114299A (en) 1998-01-14 1999-08-02 Conway-Stuart Medical, Inc. Electrosurgical device for sphincter treatment
CA2318315A1 (en) 1998-01-14 1999-07-22 Conway-Stuart Medical, Inc. Electrosurgical apparatus for treating gastroesophageal reflux disease (gerd) and method
AU2317899A (en) 1998-01-14 1999-08-02 Conway-Stuart Medical, Inc. Gerd treatment apparatus and method
US6159178A (en) * 1998-01-23 2000-12-12 Heartport, Inc. Methods and devices for occluding the ascending aorta and maintaining circulation of oxygenated blood in the patient when the patient's heart is arrested
US6802841B2 (en) 1998-06-04 2004-10-12 Curon Medical, Inc. Systems and methods for applying a selected treatment agent into contact with tissue to treat sphincter dysfunction
US6790207B2 (en) 1998-06-04 2004-09-14 Curon Medical, Inc. Systems and methods for applying a selected treatment agent into contact with tissue to treat disorders of the gastrointestinal tract
WO1999043263A1 (en) 1998-02-27 1999-09-02 Conway-Stuart Medical, Inc. Apparatus to electrosurgically treat esophageal sphincters
US7713297B2 (en) * 1998-04-11 2010-05-11 Boston Scientific Scimed, Inc. Drug-releasing stent with ceramic-containing layer
US6219577B1 (en) 1998-04-14 2001-04-17 Global Vascular Concepts, Inc. Iontophoresis, electroporation and combination catheters for local drug delivery to arteries and other body tissues
AU3672299A (en) 1998-04-30 1999-11-16 Stuart D Edwards Electrosurgical sphincter treatment apparatus
US6267747B1 (en) 1998-05-11 2001-07-31 Cardeon Corporation Aortic catheter with porous aortic root balloon and methods for inducing cardioplegic arrest
IL125424D0 (en) 1998-07-20 1999-03-12 New Technologies Sa Ysy Ltd Pacing with hemodynamic enhancement
US6440102B1 (en) 1998-07-23 2002-08-27 Durect Corporation Fluid transfer and diagnostic system for treating the inner ear
US8197461B1 (en) 1998-12-04 2012-06-12 Durect Corporation Controlled release system for delivering therapeutic agents into the inner ear
US6406455B1 (en) 1998-12-18 2002-06-18 Biovalve Technologies, Inc. Injection devices
US6955661B1 (en) 1999-01-25 2005-10-18 Atrium Medical Corporation Expandable fluoropolymer device for delivery of therapeutic agents and method of making
US6911201B1 (en) 1999-02-04 2005-06-28 Technion Research & Development Foundation Ltd. Method of producing undifferentiated hemopoietic stem cells using a stationary phase plug-flow bioreactor
US6314317B1 (en) 1999-02-18 2001-11-06 Biovalve Technologies, Inc. Electroactive pore
US8019421B2 (en) 1999-03-05 2011-09-13 Metacure Limited Blood glucose level control
US8666495B2 (en) 1999-03-05 2014-03-04 Metacure Limited Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US8700161B2 (en) 1999-03-05 2014-04-15 Metacure Limited Blood glucose level control
US9101765B2 (en) 1999-03-05 2015-08-11 Metacure Limited Non-immediate effects of therapy
US6792306B2 (en) * 2000-03-10 2004-09-14 Biophoretic Therapeutic Systems, Llc Finger-mounted electrokinetic delivery system for self-administration of medicaments and methods therefor
DE19912844A1 (en) * 1999-03-22 2000-09-28 Saphir Medical Products Gmbh Using a cutting device employing a fluid as the cutting medium, for the surgical treatment
US6425877B1 (en) * 1999-04-02 2002-07-30 Novasys Medical, Inc. Treatment of tissue in the digestive circulatory respiratory urinary and reproductive systems
US6047209A (en) * 1999-04-02 2000-04-04 Denny; Jeffrey Paul Method and apparatus for maintenance of pierced orifices
US6593130B1 (en) 1999-04-16 2003-07-15 The Regents Of The University Of California Method and apparatus for ex vivo and in vivo cellular electroporation of gene protein or drug therapy
AU4696100A (en) 1999-05-04 2000-11-17 Curon Medical, Inc. Electrodes for creating lesions in tissue regions at or near a sphincter
US7190997B1 (en) 1999-06-04 2007-03-13 Impulse Dynamics Nv Drug delivery device
US7092753B2 (en) * 1999-06-04 2006-08-15 Impulse Dynamics Nv Drug delivery device
AU4947100A (en) * 1999-06-04 2000-12-28 Impulse Dynamics N.V. Drug delivery device
US7171263B2 (en) * 1999-06-04 2007-01-30 Impulse Dynamics Nv Drug delivery device
IL141250D0 (en) * 1999-06-05 2002-03-10 Univ Leland Stanford Junior Method and composition for inhibiting cardiovascular cell proliferation
EP1218801A4 (en) 1999-09-08 2009-07-01 Mederi Therapeutics Inc Systems and methods for monitoring and controlling use of medical devices
US8845632B2 (en) 2000-05-18 2014-09-30 Mederi Therapeutics, Inc. Graphical user interface for monitoring and controlling use of medical devices
CA2384025A1 (en) 1999-09-08 2001-03-15 Curon Medical, Inc. System for controlling a family of treatment devices
AU1629001A (en) 1999-09-08 2001-04-10 Curon Medical, Inc. Systems and methods for monitoring and controlling use of medical devices
US6587718B2 (en) 1999-10-08 2003-07-01 Scimed Life Systems, Inc. Iontophoretic delivery to heart tissue
US7027863B1 (en) 1999-10-25 2006-04-11 Impulse Dynamics N.V. Device for cardiac therapy
US6993385B1 (en) 1999-10-25 2006-01-31 Impulse Dynamics N.V. Cardiac contractility modulation device having anti-arrhythmic capabilities and a method of operating thereof
WO2001030445A1 (en) 1999-10-25 2001-05-03 Impulse Dynamics N.V. Cardiac contractility modulation device having anti-arrhythmic capabilities and a method of operating thereof
WO2001035846A1 (en) 1999-11-16 2001-05-25 Ganz Robert A System and method of treating abnormal tissue in the human esophagus
US20040215235A1 (en) 1999-11-16 2004-10-28 Barrx, Inc. Methods and systems for determining physiologic characteristics for treatment of the esophagus
US20060095032A1 (en) 1999-11-16 2006-05-04 Jerome Jackson Methods and systems for determining physiologic characteristics for treatment of the esophagus
US6547776B1 (en) 2000-01-03 2003-04-15 Curon Medical, Inc. Systems and methods for treating tissue in the crura
US7184827B1 (en) * 2000-01-24 2007-02-27 Stuart D. Edwards Shrinkage of dilatations in the body
US7306591B2 (en) 2000-10-02 2007-12-11 Novasys Medical, Inc. Apparatus and methods for treating female urinary incontinence
US6640120B1 (en) 2000-10-05 2003-10-28 Scimed Life Systems, Inc. Probe assembly for mapping and ablating pulmonary vein tissue and method of using same
US7104987B2 (en) 2000-10-17 2006-09-12 Asthmatx, Inc. Control system and process for application of energy to airway walls and other mediums
US7198635B2 (en) 2000-10-17 2007-04-03 Asthmatx, Inc. Modification of airways by application of energy
DE10129285C2 (en) * 2001-06-18 2003-01-09 Hans-Joachim Mueschenborn Encryption method with arbitrarily selectable time keys
WO2003002243A2 (en) 2001-06-27 2003-01-09 Remon Medical Technologies Ltd. Method and device for electrochemical formation of therapeutic species in vivo
FR2830767B1 (en) * 2001-10-12 2004-03-12 Optis France Sa A drug delivery by iontophoresis or electroporation introculaire
US7488313B2 (en) * 2001-11-29 2009-02-10 Boston Scientific Scimed, Inc. Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment
DE10205373B4 (en) * 2002-02-09 2007-07-19 Aloys Wobben Fire protection
US20070135875A1 (en) 2002-04-08 2007-06-14 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US8150519B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Methods and apparatus for bilateral renal neuromodulation
US20080213331A1 (en) 2002-04-08 2008-09-04 Ardian, Inc. Methods and devices for renal nerve blocking
US9636174B2 (en) 2002-04-08 2017-05-02 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US7617005B2 (en) 2002-04-08 2009-11-10 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US20070129761A1 (en) 2002-04-08 2007-06-07 Ardian, Inc. Methods for treating heart arrhythmia
US8347891B2 (en) 2002-04-08 2013-01-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US7756583B2 (en) 2002-04-08 2010-07-13 Ardian, Inc. Methods and apparatus for intravascularly-induced neuromodulation
US7048714B2 (en) * 2002-10-30 2006-05-23 Biorest Ltd. Drug eluting medical device with an expandable portion for drug release
CN101261561A (en) 2003-02-10 2008-09-10 N-特莱格有限公司 Touch detection for a digitizer
WO2004080533A1 (en) 2003-03-10 2004-09-23 Impulse Dynamics Nv Apparatus and method for delivering electrical signals to modify gene expression in cardiac tissue
US8352031B2 (en) 2004-03-10 2013-01-08 Impulse Dynamics Nv Protein activity modification
US20040226556A1 (en) 2003-05-13 2004-11-18 Deem Mark E. Apparatus for treating asthma using neurotoxin
US20040236308A1 (en) * 2003-05-22 2004-11-25 Atrium Medical Corp. Kinetic isolation pressurization
US8792985B2 (en) 2003-07-21 2014-07-29 Metacure Limited Gastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
CN1867299B (en) 2003-09-12 2010-09-29 明诺医学有限公司 Selectable eccentric remodeling and/or ablation of atherosclerotic material
US9713730B2 (en) 2004-09-10 2017-07-25 Boston Scientific Scimed, Inc. Apparatus and method for treatment of in-stent restenosis
US7736362B2 (en) * 2003-09-15 2010-06-15 Boston Scientific Scimed, Inc. Catheter balloons
US7150745B2 (en) 2004-01-09 2006-12-19 Barrx Medical, Inc. Devices and methods for treatment of luminal tissue
US7922740B2 (en) 2004-02-24 2011-04-12 Boston Scientific Scimed, Inc. Rotatable catheter assembly
US7744619B2 (en) * 2004-02-24 2010-06-29 Boston Scientific Scimed, Inc. Rotatable catheter assembly
WO2005084301A2 (en) * 2004-03-01 2005-09-15 Lumen Therapeutics, Llc Compositions and methods for treating diseases
WO2006097934A2 (en) 2005-03-18 2006-09-21 Metacure Limited Pancreas lead
CA2594673A1 (en) 2004-12-09 2006-07-13 Impulse Dynamics Nv Protein activity modification
US9821158B2 (en) 2005-02-17 2017-11-21 Metacure Limited Non-immediate effects of therapy
US20050209548A1 (en) * 2004-03-19 2005-09-22 Dev Sukhendu B Electroporation-mediated intravascular delivery
US7857767B2 (en) 2004-04-19 2010-12-28 Invention Science Fund I, Llc Lumen-traveling device
US7998060B2 (en) 2004-04-19 2011-08-16 The Invention Science Fund I, Llc Lumen-traveling delivery device
US8019413B2 (en) 2007-03-19 2011-09-13 The Invention Science Fund I, Llc Lumen-traveling biological interface device and method of use
US9011329B2 (en) 2004-04-19 2015-04-21 Searete Llc Lumenally-active device
US8337482B2 (en) 2004-04-19 2012-12-25 The Invention Science Fund I, Llc System for perfusion management
US7850676B2 (en) 2004-04-19 2010-12-14 The Invention Science Fund I, Llc System with a reservoir for perfusion management
US9801527B2 (en) 2004-04-19 2017-10-31 Gearbox, Llc Lumen-traveling biological interface device
US8353896B2 (en) 2004-04-19 2013-01-15 The Invention Science Fund I, Llc Controllable release nasal system
US8361013B2 (en) 2004-04-19 2013-01-29 The Invention Science Fund I, Llc Telescoping perfusion management system
US20120035437A1 (en) 2006-04-12 2012-02-09 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Navigation of a lumen traveling device toward a target
US7706873B2 (en) * 2004-05-05 2010-04-27 Mario Ammirati System and method for controlled delivery of a therapeutic agent to a target location within an internal body tissue
US8092549B2 (en) 2004-09-24 2012-01-10 The Invention Science Fund I, Llc Ciliated stent-like-system
US20060085058A1 (en) * 2004-10-20 2006-04-20 Rosenthal Arthur L System and method for delivering a biologically active material to a body lumen
WO2006052940A2 (en) 2004-11-05 2006-05-18 Asthmatx, Inc. Medical device with procedure improvement features
US7949407B2 (en) 2004-11-05 2011-05-24 Asthmatx, Inc. Energy delivery devices and methods
EP1819304A4 (en) 2004-12-09 2015-04-15 Twelve Inc Aortic valve repair
WO2006119467A2 (en) 2005-05-04 2006-11-09 Impulse Dynamics Nv Protein activity modification
US10064540B2 (en) 2005-02-02 2018-09-04 Intuitive Surgical Operations, Inc. Visualization apparatus for transseptal access
US9055906B2 (en) 2006-06-14 2015-06-16 Intuitive Surgical Operations, Inc. In-vivo visualization systems
US7860555B2 (en) 2005-02-02 2010-12-28 Voyage Medical, Inc. Tissue visualization and manipulation system
US7918787B2 (en) 2005-02-02 2011-04-05 Voyage Medical, Inc. Tissue visualization and manipulation systems
US8221310B2 (en) 2005-10-25 2012-07-17 Voyage Medical, Inc. Tissue visualization device and method variations
US7860556B2 (en) 2005-02-02 2010-12-28 Voyage Medical, Inc. Tissue imaging and extraction systems
US8137333B2 (en) 2005-10-25 2012-03-20 Voyage Medical, Inc. Delivery of biological compounds to ischemic and/or infarcted tissue
US9510732B2 (en) 2005-10-25 2016-12-06 Intuitive Surgical Operations, Inc. Methods and apparatus for efficient purging
US8050746B2 (en) 2005-02-02 2011-11-01 Voyage Medical, Inc. Tissue visualization device and method variations
US8078266B2 (en) 2005-10-25 2011-12-13 Voyage Medical, Inc. Flow reduction hood systems
US7930016B1 (en) 2005-02-02 2011-04-19 Voyage Medical, Inc. Tissue closure system
US20120149985A1 (en) * 2007-05-18 2012-06-14 Frassica James J Rotate-to-advance catheterization system
SE0501077L (en) 2005-05-12 2006-11-13 Spectracure Ab Device for photodynamic diagnosis or treatment
WO2006133193A1 (en) * 2005-06-07 2006-12-14 American Medical Systems Research Corporation Injection guidance system and method
JP2007000342A (en) * 2005-06-23 2007-01-11 Transcutaneous Technologies Inc Iontophoresis device for controlling quantity and time of dosing a plurality of medicaments
US8295922B2 (en) 2005-08-08 2012-10-23 Tti Ellebeau, Inc. Iontophoresis device
US8386030B2 (en) 2005-08-08 2013-02-26 Tti Ellebeau, Inc. Iontophoresis device
US20070088332A1 (en) * 2005-08-22 2007-04-19 Transcutaneous Technologies Inc. Iontophoresis device
JPWO2007023907A1 (en) * 2005-08-24 2009-02-26 Tti・エルビュー株式会社 Frozen type iontophoresis electrode structure
JPWO2007026672A1 (en) * 2005-08-29 2009-03-05 Tti・エルビュー株式会社 Iontophoretic versatility electrolyte composition
JPWO2007029611A1 (en) * 2005-09-06 2009-03-19 Tti・エルビュー株式会社 Iontophoresis device
US20070112294A1 (en) * 2005-09-14 2007-05-17 Transcutaneous Technologies Inc. Iontophoresis device
CA2619665A1 (en) 2005-09-15 2007-03-22 Tti Ellebeau, Inc. Rod type iontophoresis device
WO2007041323A1 (en) * 2005-09-30 2007-04-12 Tti Ellebeau, Inc. Iontophoretic delivery of vesicle-encapsulated active agents
EP1928542A1 (en) * 2005-09-30 2008-06-11 Tti Ellebeau, Inc. Method and system to detect malfunctions in an iontophoresis device that delivers active agents to biological interfaces
WO2007041434A2 (en) * 2005-09-30 2007-04-12 Tti Ellebeau, Inc. Iontophoresis apparatus and method for delivery of angiogenic factors to enhance healing of injured tissue
EP1944057A4 (en) * 2005-09-30 2009-02-18 Tti Ellebeau Inc Iontophoresis apparatus capable of controlling dose and timing of administration of sleep inducer and analeptic agent
US20070093802A1 (en) 2005-10-21 2007-04-26 Danek Christopher J Energy delivery devices and methods
US7959627B2 (en) 2005-11-23 2011-06-14 Barrx Medical, Inc. Precision ablating device
US7997278B2 (en) 2005-11-23 2011-08-16 Barrx Medical, Inc. Precision ablating method
US8702694B2 (en) 2005-11-23 2014-04-22 Covidien Lp Auto-aligning ablating device and method of use
US8840660B2 (en) 2006-01-05 2014-09-23 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8089029B2 (en) 2006-02-01 2012-01-03 Boston Scientific Scimed, Inc. Bioabsorbable metal medical device and method of manufacture
US20070224235A1 (en) 2006-03-24 2007-09-27 Barron Tenney Medical devices having nanoporous coatings for controlled therapeutic agent delivery
US8888684B2 (en) * 2006-03-27 2014-11-18 Boston Scientific Scimed, Inc. Medical devices with local drug delivery capabilities
US8187620B2 (en) 2006-03-27 2012-05-29 Boston Scientific Scimed, Inc. Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents
US8048150B2 (en) 2006-04-12 2011-11-01 Boston Scientific Scimed, Inc. Endoprosthesis having a fiber meshwork disposed thereon
US8019435B2 (en) 2006-05-02 2011-09-13 Boston Scientific Scimed, Inc. Control of arterial smooth muscle tone
US8815275B2 (en) 2006-06-28 2014-08-26 Boston Scientific Scimed, Inc. Coatings for medical devices comprising a therapeutic agent and a metallic material
US8771343B2 (en) 2006-06-29 2014-07-08 Boston Scientific Scimed, Inc. Medical devices with selective titanium oxide coatings
US20100063585A1 (en) * 2006-07-03